The following prior art references are considered as being relevant for an understanding of the invention.
Atlas E, Yizhar Z, Khamis S, Slomka N, Hayek S, Gefen A. Utilization of the foot load monitor for evaluating deep plantar tissue stresses in patients with diabetes: Proof-of-concept studies. Gait Posture, 29:377-82, 2009.
Gefen A. 2003. Plantar soft tissue loading under the medial metatarsals in the standing diabetic foot. Med Eng Phys. 25:491-9.
Krishnan S T M, Rayman G. 2004. The LDlflare: A novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes. Diabetes Care 27: 2930-5.
van Schie C H. 2005. A review of the biomechanics of the diabetic foot. Int J Low Extrem Wounds. 4:160-70.
U.S. Pat. No. 4,653,507 to Laudio.
U.S. Pat. No. 5,191,896 to Gafni.
U.S. Pat. No. 5,007,433 to Hersdorffer.
U.S. Pat. No. 5,666,963 to Swenson et al.
U.S. Pat. No. 6,090,050 to Constantinides.
Diabetic neuropathy is a peripheral nerve disorder caused by diabetes and is considered to be the most common serious complication of the disease. Diabetic neuropathy typically evolves in multiple locations, and induces damage to numerous peripheral nerves. Pathological changes to the nerves occur both in the body of axons and in myelin sheaths. Initially, the axons become thin and the myelin sheaths start to disintegrate, thereby slowing the conduction velocity in the affected nerves. Subsequently, the complete nerve structure is atrophied. While these changes occur systematically across the nervous system, they are most profound in the distal regions of the somatic nerves. This condition is referred to as poly-neuropathy and affects the arms, hands, fingers, legs, and feet. Loss of sensation in the feet is the most common symptom. This loss of sensation is manifested in numbness or insensitivity to pain or temperature. The loss of sensation in the feet is associated with progressive foot deformities, such as hammertoes and the collapse of the midfoot. Blisters and ulcers may appear on numb areas of the foot because sustained mechanical loading (pressure, shear) and even actual injury go unnoticed. If foot injuries are not treated promptly, infection may occur that spreads sub-dermally and into the bone. Sustained mechanical loads in deep tissues also occur, and may lead to ulcers (Gefen, 2003; Atlas et al., 2009). Progressive ulcers often require amputation of the toes or the entire foot.
Diabetic foot ulcers are relatively common, and are estimated to occur in 15% of the diabetic population, which is estimated at about 150 million people worldwide today. It is estimated that half the amputations caused by diabetic neuropathy are preventable when minor problems are caught and treated in time, particularly if the patient is aware of his/her neuropathy condition.
Apart from foot ulcers, the continuous numbness and tingling of the hands and feet also decrease the quality of life for patients with diabetes. Unfortunately, at present, once nerve damage occurs, it is irreversible. Symptoms are often minor at first, and because most nerve damage occurs over several years, mild cases may go unnoticed for a long time, but can suddenly become severe. The key issue in managing diabetes in general, and in managing diabetic neuropathy in particular, is prevention of further damage to tissues and organs by using medications and a diet to control the level of glucose and avoid hyperglycemia.
The clinical practice for preventing diabetic foot ulcers is to protect the feet by prescribing high quality, well fitting footwear, preferably custom-made footwear. In order for this approach to work, patients at risk need to be identified, and their footwear needs to be carefully designed to protect the most vulnerable regions on the patient's feet by re-distributing mechanical loads onto other, less susceptible foot areas. This is commonly done by first measuring pressures under the patient's feet. However, it is the localization of neuropathy, as opposed to the level of pressure, which is the most important predictor of possible ulceration (van Schie, 2005).
Screening for the presence of neuropathy using standard, simple clinical tools, such as the neuropathy disability score, neuropathy symptom score, pressure perception using Semmes-Weinstein monofilaments and vibration sensation with the neurothesiometer (marketed by Horwell Scientific Laboratory Supplies, Nottingham, UK) has been shown to be important in identifying individuals at risk for foot ulceration. However, these tools assess mainly large fiber function (Krishnan and Rayman, 2004). It has been suggested that small unmyelinated C-fibers, which are responsible for sensating heat (responsive from 30 to over 45° C.), may be selectively damaged in the early stages of diabetes (Krishnan and Rayman, 2004).
The most commonly used method for diagnosing peripheral neuropathy today is the Semmes-Weinstein method. As known in the art, the Semmes-Weinstein monofilament consists of a nylon filament embedded in a plastic handle that is used to assess semi-quantitatively the threshold sensitivity for light touch by exploiting physical properties of a buckling column to theoretically generate a force independent of the force applied to the handle. The actual pressure delivered to the skin surface in fact varies with the angle between the filament and the skin. Moreover, the friction between the filament and skin is not considered in the measurement, but may vary considerably among individuals, thereby introducing an inherent error into these measurements. Most importantly, the Semmes-Weinstein monofilament test is able to estimate a rough range of sensitivities, as opposed to a specific sensitivity of the individual.
An alternative method applies a two-point static touch to the skin surface. This test measures how far apart two separate touch points need to be for the touch points to be perceived as two distinct points. The tip of the test device is composed of two parallel pin pricks whose separation can be adjusted. Like the Semmes-Weinstein test, the two point test is affected by the orientation of the pricks with respect to the skin, and by the friction between the device and the skin. Also, the sensation threshold depends on the magnitude of pressure applied by the examiner over the tested tissue region.
Another method uses a calibrated tuning fork or a vibration perception threshold meter (biothesiometer). The volume of vibration of a vibrating tip attached to the skin is raised until the patient feels the vibration. The vibration perception threshold is measured in volts. The major problem with the biothesiometer devices is that they produce a wave, as opposed to a local stimulus. The vibratory wave propagates over a relatively large area of skin and subcutaneous tissues, thereby making it extremely difficult to identify the location of the most severe neuropathy, where tissues need to be protected.
Another method uses a pen-shaped device having a polymer surface and a metal alloy surface. The polymer surface feels warmer than the metal alloy due to the difference in thermal conductivity of the materials. The examiner randomly places one of the two surfaces on the top of the patient's foot and asks whether it feels cold or not so cold at that particular spot. This does not provide a quantitative reading, and therefore does not allow systematic comparisons with normative databases. Additionally, because the device is a passive thermal element, its performance will depend on ambient conditions (the manufacturer recommends using it in a room below 23° C.). Since the device is pressed against the patients' skin during examination, the local perception of temperature is masked by the perception of pressure. A commercially available device that uses this method is the “tip-therm”® device (by tip therm GmbH).
Another method uses a single heat stimulator that is strapped around a specific location on the foot or hand (e.g. using Velcro straps wrapped around the foot or hand). Once fixated and turned on, the stimulator heats up to a pre-determined temperature which can be adjusted, usually up to 50° C. A patient response device, typically containing press-buttons labeled “Yes” and “No”, is used by the patient to indicate whether or not he can feel the warm sensation, and if yes, for how long, which is the time during which the “Yes” button is pressed. The output of the system is a comparison of the time during which heating was actually applied by the stimulator strapped to the skin, against the time length of stimulation reported by the patient. The single stimulator only provides a measure of the neuropathy at the specific spot where it is attached, and so, neuropathic sites could be missed. Also, the stimulator is mechanically strapped to the skin, which induces uncontrolled mechanical loads on the examined area (and these loads are also not necessarily physiological). The temperature sensation is therefore often masked by the pressure sensation because of the strapping. Examples for commercial devices employing this method are the Computer Aided Sensory Evaluator—IV (CASE IV) (WR Medical Electronics, Stillwater, Minn., USA) and the TSA-II NeuroSensory Analyzer (Medoc Advanced Medical Systems, Ramat Vishay, Israel).
Another method for detecting peripheral neuropathy is to test the responsiveness of the sweat glands of the feet, which cease to function normally when neuropathy develops. This is done by employing a chemical reaction of cobalt salt (CoCl2) with moisture. If moisture from sweat exists, a pad containing CoCl2 that is adhered to a spot on the plantar foot changes color from blue to pink. This is a qualitative indicator rather than quantitative, that the assessment of neuropathy is indirect, i.e. no actual sensation is measured. The indication is limited to the spot where the pad is located, and that the test is biased by humid environments. A commercial product that uses this method is the Neuropad® (miro Verbandstoffe, Wiehl-DrabenderhOhe, Germany).
Thus, existing devices that apply a thermal stimulus on the skin to assess neuropathy are either hand-held (e.g. the Semmes-Weinstein, the two-point touch, the biothesiometer devices) or strapped to the skin surface (e.g. the TSA-II system). With these devices, the force, angle of application and speed at which they are used to assess the neuropathy, are highly variable among examiners.
U.S. Pat. No. 4,653,507 to Laudio discloses a device comprising a first thermal conductive sensing plate having a fixed temperature and a second thermal conductive sensing plate having a controllable temperature. The plates are applied to the skin and the threshold temperature differential between the plates is determined.
U.S. Pat. No. 5,191,896 to Gafni et al discloses an apparatus in which sensory stimulation is applied to a patient in accordance with any one of several protocols.
U.S. Pat. No. 5,007,433 to Hersdorffer discloses a pressure stimulator configured to apply a selectable pressure to a skin surface.
U.S. Pat. No. 5,666,963 to Swenson et al discloses a hand-held device which is translated or rolled over a skin surface. The contact surface on the device is made of a high thermal conductivity material, and when the device is at room temperature, a cooling sensation is experienced by the subject except in those regions where nerve sensation is abnormally low.
U.S. Pat. No. 6,090,050 to Constantinides discloses a device for recording temperatures on a skin surface.
Prior art devices evaluate temperature perception of the skin at a single site per examination. Hand-held stimulators tend to be inaccurate because the pressure applied to the skin surface varies from user to user which often affects the local perception of temperature changes.